Lumen Morphology And Vascular Resistance Measurements Data Collection Systems Apparatus And Methods

ABSTRACT

A method and apparatus of automatically locating in an image of a blood vessel the lumen boundary at a position in the vessel and from that measuring the diameter of the vessel. From the diameter of the vessel and estimated blood flow rate, a number of clinically significant physiological parameters are then determined and various user displays of interest generated. One use of these images and parameters is to aid the clinician in the placement of a stent. The system, in one embodiment, uses these measurements to allow the clinician to simulate the placement of a stent and to determine the effect of the placement. In addition, from these patient parameters various patient treatments are then performed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/549,814, filed on Aug. 23, 2019, which is continuation of U.S. patentapplication Ser. No. 13/796,710 filed on Mar. 12, 2013, which is acontinuation of U.S. application Ser. No. 12/888,347, filed on Sep. 22,2010 (now U.S. Pat. No. 9,138,147), which claims priority to and thebenefit of U.S. Provisional Application No. 61/244,992, filed on Sep.23, 2009, and U.S. Provisional Application No. 61/334,834, filed on May14, 2010, the disclosures of which are incorporated herein by reference.

FIELD OF INVENTION

This invention relates generally to the field of optical coherencetomographic imaging and more specifically to optical coherencetechniques for diagnosing and treating vascular stenoses.

BACKGROUND OF THE INVENTION

Coronary artery disease is one of the leading causes of death worldwide.The ability to better diagnose, monitor, and treat coronary arterydiseases can be of life saving importance. Intravascular opticalcoherence tomography (OCT) is a catheter-based imaging modality thatemploys safe, non-ionizing near-infrared light to peer into coronaryartery walls and present images valuable for the study of the vascularwall architecture. Utilizing broad-band coherent light, interferometry,and micro-optics, OCT can provide video-rate in-vivo tomography within adiseased vessel with resolution down to the micrometer level. This levelof detail enables OCT to diagnose as well as monitor the progression ofcoronary artery disease.

The quantitative assessment of vascular pathology and its progressioninvolves the calculation of different quantitative measures such as thevessel cross-sectional area, mean diameter, and blood flow resistance,all of which rely on the accurate identification of the luminal border.While the luminal border in OCT images is clearly identifiable by thehuman eye, it is tedious, expensive, and time consuming to manuallytrace the luminal border. Thus there is a need for a reliable techniquethat can automatically identify the luminal border.

OCT produces images that are higher in resolution and contrast comparedto those of intravascular ultrasound (IVUS). As opposed to IVUS whichimages through blood, OCT images are typically acquired with bloodcleared from the view of the optical probe. This is one reason theluminal border in OCT images is sharper and more defined compared tothat in IVUS images.

Cross-sectional diameter and area measurements provide interventionalcardiologists with useful guidance for stent sizing and placement.However, the relationship of these geometric measurements to clinicallyrelevant variables, such as ability of the artery to supply an adequateflow of blood to the myocardium when metabolic demands are high, is notwell understood. In early studies, the percent stenosis of an individualcoronary lesion measured by angiography was found to be a relativelypoor predictor of the physiological significance of the lesion. Incontrast, several later studies demonstrated that lumen measurementsmade by quantitative coronary angiography (QCA) and IVUS correlateclosely with physiologic measurements of coronary obstruction, includingcoronary flow reserve (CFR) and fractional flow reserve (FFR). Forexample, several studies found a high correlation between area stenosis,measured by QCA, and CFR measured by a Doppler flow wire. It appearsthat the standard angiographic (and IVUS) measures of lesionseverity—the minimum lumen area (MLA), percentage stenosis, and lesionlength—do indeed convey physiologically relevant information. However,the value of any single geometrical measure as an independent predictorof the physiological significance of a lesion in a wide patientpopulation is not clear.

Several factors contribute to the limitation of standard angiographicand IVUS lumen measurements for assessment of the physiologicalsignificance of coronary stenoses. First, the accuracy andreproducibility with which cross-sectional areas can be measured withangiography, which generally has a spatial resolution of 0.2-0.4 mm, arerelatively low. The angle of the X-ray projection, in addition to theshadowing effect of lesions with irregular contours, can increase errorssignificantly beyond the theoretical minimums. Even state-of-the-artIVUS imaging systems, which have resolutions of approximately 0.15 mm inthe axial dimension and 0.3 mm in the angular dimension, cannotaccurately measure the cross-sectional areas of small eccentric lesionsor lesions with irregular borders.

Second, the hemodynamic effects of a lesion depend on local variationsof its cross-sectional area integrated over the entire length of alesion. Therefore, the minimum cross sectional area alone isinsufficient to characterize the pressure drop across a lesion at agiven flow rate, especially in patients with diffuse coronary disease.

Third, when assessing the physiological significance of a lesion and thepotential value of revascularization, it is important to know therelative areas of the reference and stenotic segments, in addition tothe absolute value of the minimum lumen area. No single geometricalmeasure in clinical use today conveys information about both percentstenosis and MLA.

Fourth, the flow resistance or pressure drop caused by an incrementalsegment of a lesion depends on its shape as well as its cross-sectionalarea and length. Especially at high blood flow rates, the eccentricityand local slope of the walls of the artery can influence the effectiveresistance of a lesion, because losses due to flow separation andturbulence depend on local flow velocity.

Finally, in certain patients, the flow reserve of the myocardiumsupplied by the vessel can be low, due to microvascular disease, flowthrough collateral branches, or capillary shunts within infarctedmyocardium. Therefore, even if the vascular resistance of a lesion inthe vessel is high, revascularization may be contraindicated, becausethe pressure drop across the lesion may be clinically insignificant.

Intravascular OCT imaging, applied in combination with new clinicalparameters based on advanced analysis of lesion morphology, has thepotential to overcome many of the limitations of conventional measuresof lesion severity based on angiography and IVUS. The high resolution ofOCT enables accurate measurement of the shape and dimensions of thevessel lumen over the length of the lesion and its adjacent referencesegments. Furthermore, advanced models of flow dynamics enable thephysiological significance of lesions to be estimated under both normaland hyperemic conditions. It should be realized, however, that theclinical value of quantitative lesion morphology measurements—even whenaccurate—may be limited by physiological conditions in certain patients.Finally, high-frequency OCT imaging has the advantage that it canprecisely delineate three-dimensional contours of long segments ofcoronary arteries in a few seconds to assist cardiologists in theirreal-time diagnosis and treatment during PCI procedures.

In spite of advances in intravascular imaging, cardiologists frequentlydo not take full advantage of the capabilities of OCT and IVUS forplanning and evaluating stent deployment, because the measurementscurrently derived from the images provide insufficient information topredict the effectiveness of treatment. For example, many cardiologistsrely on minimum lumen area (MLA) as a key variable in their stentingdecisions. If MLA measurements are sufficiently low, the cardiologistmay decide to implant a stent. Based on the diameters and locations ofreference vessel segments, the cardiologist must then choose the properposition, length, and diameter of the stent. The wrong choice of thesize or location of the stent may lead to the failure to restore bloodflow and may even cause potentially serious clinical complications, suchas stent migration, stent thrombosis, or dissection of the vessel wall.There is a need for new methods for optimization of stent sizing andpositioning based on measurements derived from intravascular images. Toachieve maximum clinical benefit, these new methods should enablecardiologists to predict the potential physiological consequences ofimplanting stents of different diameters and lengths in differentlocations.

The present invention addresses these needs.

SUMMARY OF THE INVENTION

In one aspect, the invention relates to an automated computer-basedmethod of evaluating a region of a lumen. The method comprises the stepsof collecting a set of data regarding a vessel segment of length L usingan optical coherence tomography system, the set comprising a pluralityof cross sectional areas at a plurality of positions along the length;determining a vascular resistance ratio (VRR) using a processor and atleast a portion of the set of data; and determining a characteristic ofat least a portion of the region disposed along the length L in relationto the vascular resistance ratio.

In one embodiment, the method is applied to the region that contains astenotic lesion. In another embodiment, the method further comprises thestep of displaying at least one numerical or graphical measure of stentlength used to treat the stenotic lesion. In yet another embodiment, thestep of determining the vascular resistance ratio is performed using alumped resistor model.

In another aspect, the invention relates to a method for automaticallyidentifying the luminal border in an in-situ OCT vascular image. In oneembodiment, the method comprises the steps of generating a mask of theOCT lumen image using a computer; defining a plurality of scan lines inthe mask; identifying a region as tissue on each scan line; definingcontour segments in response to the plurality of scan lines and theregion of tissue on each scan line; identifying valid neighboringcontour segments; interpolating missing contour data between validneighboring contour segments; assessing the likely correctness of thecomputed contour and indicating to the user on which image frames thecomputed contour may require manual adjustment.

In one embodiment, the method includes the step of detecting andremoving guide wire and similar artifacts. In another embodiment, theidentification of a tissue region includes the steps of finding aplurality of start/stop pairs on each scan line; calculating thicknessand gap of each said start/stop pair; calculating a weight based on saidthickness and said gap; and defining the tissue region based on thelargest weight of tissue and gap. In another embodiment, the step ofdefining connected contour includes finding the scan line with thelargest weight; searching for discontinuities in both directions fromthe scan line to define a valid segment; and identifying the root of thecontour as the longest of the valid segments. In still yet anotherembodiment, the step of identifying valid neighboring contour includesfinding the nearest clockwise and counter-clockwise neighbors of each ofthe contour segments that pass angular, radial, and Euclidean distancethresholds.

In another embodiment, the step of detection and removal of guide wireshadow artifact comprises the steps of clearing an image binary mask byfitting an ellipse to the foreground data of the mask and blanking thearea inside ellipse; building an intensity profile using the clearedmask; identifying the guide wire shadow region in the intensity profile;detecting a guide wire offset within the shadow region; collecting themidpoint of detected guide wires on all frames; building a minimumspanning tree using the collected midpoints; and pruning the resultingminimum spanning tree to remove outliers resulting from non-guide wireshadows. In another embodiment, the step of interpolating missing dataincludes the steps of identifying required interpolation control pointswith valid contour data on both ends of the missing contour segment; andusing the control points to interpolate the missing contour segment. Instill yet another embodiment, the steps are performed on all missingcontour segments that need to be interpolated. In yet anotherembodiment, the step of searching for discontinuities comprises thesteps of calculating a scan line-to-scan line offset change histogram;smoothing said histogram; identifying the smallest change with zerocount from the histogram; and using the smallest change as a continuitymeasure.

In another embodiment, the step of evaluating the correctness of thecomputed contour comprises the steps of computing an “Error Measure” byfitting an ellipse to the computed contour; computing the root meansquare error between the computed contour and the fitted ellipse;normalizing the root mean square error to the average diameter of theellipse; and multiplying the normalized root mean square error by theratio of the number of scan lines where the lumen was successfullydetected to the total number of scan lines in the image frame. Inanother embodiment, the resulting Error Measure parameter is compared toa threshold and, for image frames where the threshold is exceeded, theuser is notified that manual contour correction may be required. In yetanother embodiment, the notification can take the form of “alert frames”drawn on a longitudinal display of the images of the pullback region.

In another aspect, the invention relates to an automated method forquantifying a vascular resistance including the steps of selectingproximal and distal frames of an OCT image; calculating actual vascularresistance of the vascular segment enclosed by said proximal and thedistal frames; calculating a total vascular resistance of the vascularsegment; and calculating vascular resistance ratio using the actualvascular resistance and said total vascular resistance. In oneembodiment, the step of calculating actual vascular resistance comprisesthe steps of extracting luminal contours of all frames enclosed by theproximal and the distal frames inclusive; calculating cross-sectionalareas from the extracted contours; constructing a smooth area graph; andusing the smooth area graph in the actual vascular resistancecalculation. In another embodiment, the step of calculating the totalvascular resistance comprises the steps of: fitting a shape between saidproximal and said distal frames; and calculating cross-sectional areasof the shape at all frame positions enclosed by the proximal and thedistal frames inclusive. In yet another embodiment, the step ofconstructing a smooth area graph includes the steps of constructing agraph using the cross-sectional areas; interpolating missing area valueson the graph; and smoothing the resulting graph. In still yet anotherembodiment, vascular resistance is calculated by computational fluiddynamics from the detected three-dimensional luminal border between theproximal and distal planes.

Another aspect of the invention is a method of placing a stent includingthe steps of: (a) measuring the parameters in the region of interest inan OCT image of a vessel; (b) simulating the placement of the stent inthe region of interest; (c) recalculating the parameters in the regionof interest; and repeating Steps b and c until the desired result isobtained.

BRIEF DESCRIPTION OF DRAWINGS

The invention is pointed out with particularity in the appended claims.The advantages of the invention described above, together with furtheradvantages, may be better understood by referring to the followingdescription taken in conjunction with the accompanying drawings. In thedrawings, like reference characters generally refer to the same partsthroughout the different views. The drawings are not necessarily toscale, emphasis instead generally being placed upon illustrating theprinciples of the invention.

FIG. 1A is a generalized schematic of an OCT data collection systemhaving an imaging probe disposed in a vessel of interest;

FIG. 1B is an example of a sample detected contour interpolatedaccording to an illustrative embodiment of the invention;

FIG. 2 is an example of a sample detected contour with guide wire andside branch missing data interpolated according to an illustrativeembodiment of the invention;

FIG. 3 is an example of a sample area graph after smoothing according toan illustrative embodiment of the invention;

FIG. 4 is an example of an alternative display in which the meancross-sectional diameters and “Alert Frame” feedback are shown in aseparate panel above the OCT L-mode image according to an illustrativeembodiment of the invention;

FIG. 5 is an example of a 3D display of the shape of the lumen of avessel reconstructed from an OCT image in which lumen contours weretraced automatically according to an illustrative embodiment of theinvention;

FIG. 6a is a flow chart of an embodiment of the method to detect theshape of the lumen of the vessel OCT image according to an illustrativeembodiment of the invention;

FIG. 6b is a diagram of start/stop pairs on scan lines according to anillustrative embodiment of the invention;

FIGS. 7a and b are samples of an OCT image and its resulting medianmask, respectively, according to an illustrative embodiment of theinvention;

FIG. 8 is a diagram of a scan line with multiple start/stop pairsaccording to an illustrative embodiment of the invention;

FIG. 9 is a diagram of a discontinuity search according to anillustrative embodiment of the invention;

FIG. 10 is a histogram depicting a line-to-line change according to anillustrative embodiment of the invention;

FIG. 11a is a sample of a median mask before clearing according to anillustrative embodiment of the invention;

FIG. 11b is a sample image of a median mask after clearing according toan illustrative embodiment of the invention;

FIG. 11c is a sample image of intensity profile according to anillustrative embodiment of the invention;

FIG. 11d is a sample image of a minimum spanning tree before pruningaccording to an illustrative embodiment of the invention;

FIG. 11e is a sample image of a minimum spanning tree after pruningaccording to an illustrative embodiment of the invention;

FIG. 12 is an example of a sample area graph without smoothing accordingto an illustrative embodiment of the invention;

FIG. 13 is a lumped parameter model of the blood flow resistances in aportion of a coronary artery;

FIG. 14 is an exemplary model geometry for calculation of VRR accordingto an embodiment of the invention;

FIG. 15 is an example of cylindrically symmetric computational flowgeometry on which a second embodiment of the invention is based;

FIG. 16 is an example of a full 3D computational flow geometry on whicha third embodiment of the invention is based;

FIG. 17 is an example of a 3D display in which the contiguous length ofan artery that encompasses a fixed fraction of the total resistancebetween user-adjustable proximal and distal reference planes ishighlighted;

FIG. 18 is an example of a 3D display in which all incremental segmentsof the artery that encompasses a fixed fraction of the total resistancebetween user-adjustable proximal and distal reference planes arehighlighted;

FIGS. 19a and 19b are examples of embodiments of a longitudinal displayof the mean diameter of a coronary artery in which the arterial branchesare shown as rectangular protrusions with widths proportional to thediameters of the ostia of the branches and as circular regions withdiameters proportional to the diameters of the ostia of the branches,respectively;

FIG. 20 is an example of an embodiment of a longitudinal display of themean diameter of a coronary artery that includes the profile of asuperimposed stent;

FIG. 21 is a flow diagram of an embodiment of a method for stentdiameter and position optimization based on a user-selected stentlength;

FIG. 22 is a flow diagram of an embodiment of a method for stentdiameter, length, and position optimization based on a user-selectedmaximum value of the post-stent VRR;

FIG. 23 is an example of a total pressure versus distance graph asproduced by a calculation method using fluid dynamics according to anillustrative embodiment of the invention;

FIG. 24 depicts a schematic diagram of an equivalent resistor network ofthe pressure drops through the artery according to an illustrativeembodiment of the invention;

FIGS. 25a and 25b are examples showing the pre- and (predicted)post-stented mean-diameter lumen profiles, respectively, resulting fromoptimization according to one embodiment of the invention; and

FIGS. 26a and 26b are examples showing the pre- and (predicted)post-stented mean-diameter lumen profiles, respectively, resulting fromoptimization according to another embodiment of the invention; and

FIG. 27 is a software-based user interface showing a longitudinal OCTimage in the bottom, a cross sectional view on the right, and the degreeof stent malapposition in three dimensions in the top according to anillustrative embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1a is a high level schematic diagram depicting components of an OCTsystem 10 constructed in accordance with the invention. FIG. 1a ishighly generalized and not to scale. A vessel of interest 20 defining alumen having a wall 21 is imaged using catheter 25 having a catheterportion having an optical fiber-based imaging probe 30 disposed therein.The catheter 25 includes a flushing subsystem having flush ports 32. Theflushing system can be of any suitable type or variety that displaces asufficient amount of blood such that in vivo OCT data collection canproceed using the probe 30. The system 10 includes an OCT system orsubsystem 36 that connects to the imaging probe 30 via an optical fiber.The OCT system or subsystem 36 can include a light source such as alaser, an interferometer, various optical paths, a clock generator,photodiodes, and other OCT system components.

In one embodiment a computer or processor is part of the OCT system 36or is included as a separate subsystem 40 in electrical communicationwith the OCT system 36. The computer or processor 40 includes memory,storage, buses and other components suitable for processing data. forlumen detection and pull back data collection as discussed below. In oneembodiment, the computer or processor includes software implementationsor programs 41 of the methods described herein that are stored in memoryand execute using a processor. A display 42 is part of the overallsystem 10 for showing cross-sectional scan data as longitudinal scans orin other suitable formats.

In brief overview, the present invention provides a method and apparatusof automatically locating a lumen boundary at a position in a vessel ofinterest (using an OCT image or the underlying data) and from thatmeasuring the diameter of the vessel. From the diameter of the vesseland calculated blood flow rate a number of clinically significantphysiological parameters are then determined and various images ofinterest generated. One use of these images and parameters is to aid theclinician in the placement of a stent. The system, in one embodiment,uses these measurements to allow the clinician to simulate the placementof a stent and determine the effect of the placement. In addition, fromthese patient parameters various patient treatments are then performed.

As a first step, the system determines the lumen boundary. Generally,data taken by an OCT system is used with the methods described herein torecognize and avoid residual blood, guide wire reflections, and otherstructures that may appear to be part of the vessel wall. Interpolationof a continuous boundary is accomplished by imposing continuity of theinner surface of the vessel across neighboring frames. FIGS. 1 and 2show examples of lumen contours drawn automatically by the softwarebased method on two frames of a frequency domain OCT (FD-OCT) imagesequence. To help the user identify stenotic and normal vessel segments,in one embodiment the software shows the cross-sectional areascalculated automatically for all frames in a sequence as a graphsuperimposed on the longitudinal (L)—mode image (FIG. 3). The lines 10,10′ indicate the position of the user-selected proximal and distalreference frames. An alternative embodiment of the display shows themean diameter values profile in a separate panel above the L-modedisplay (FIG. 3). FIG. 4 shows an alternative display in which the meancross-sectional diameters and an “Alert Frame” feedback are shown in aseparate panel above the OCT L-mode. The alert frame, labeled AFindicates a frame where the system believes human intervention isrequired to verify the values shown.

The mean diameter of each cross-section is calculated either as thediameter of a circle with an area equal to that of the cross section oras the mean of the chord lengths at all angles drawn through thecentroid of the lumen cross-section. In one embodiment, the minimumlumen area (MLA), proximal and distal reference areas, percent diameterstenosis, and the length between references are displayed numerically inthe same panel.

In one embodiment, the system then also generates a three-dimensionalrendering of the shape of the vessel lumen as calculated from thecross-sectional measurements. An example is shown in FIG. 5. The usersets the positions of the proximal and distal reference planes manuallyon the 3D image by dragging either line marker in the L-mode display orreference planes on the 3D display. The longitudinal position betweenthe reference markers at which the cross-sectional area is smallest isfound automatically and a separate marker plane is placed automaticallyby the computer at this position. In one embodiment, the entire displaycan be rotated around the longitudinal axis by steering a compass wheelin the display.

Referring to FIG. 6a , the method of detecting the lumen of a vessel inan OCT image is briefly described. First an image mask is created. Inone embodiment, the image mask is a binary image mask to demark thegeneral contour of the lumen wall. Next, a list of weighted tissueregions is created and potential contours defined. Discontinuities inthese contours are rejected and the longest remaining contour selected.Any artifacts such as the shadow of the guidewire are removed andmissing contour data is interpolated to correct for missing portions ofthe image.

In more detail and referring to FIG. 6b , the smallest data unit in anOCT image is called a sample. A sequence of samples along a ray 20originating at the catheter center to the maximum imaging depth iscalled a scan line. An OCT image is typically acquired one scan line ata time. A cross-sectional image is formed by a collection of scan linesas the OCT catheter rotates. Further, to image a segment of the vessel,the catheter is moved longitudinally along the vessel while rotating,hence acquiring a set of cross-sectional images in a spiral pattern. Itshould be noted that while the present invention is described in thecontext of OCT images, the present invention is not so limited. Thus,for example, identifying any border, boundary, or contour in anyvascular image is within the spirit and scope of the present invention.

A cross-sectional image of the vessel is created for each completerotation of the optical probe. These images are individuallypreprocessed and a suitable threshold is applied to create a binaryforeground/background image mask, wherein the foreground is defined tocontain the potentially relevant image information (e.g. the vesselwall) and the background represents the empty luminal space between thecatheter and vessel wall, as well the ‘noise floor’ beyond the deepestimaging depth within the wall. The image mask is further processed byconvolving the image mask with a median filter that has a suitable widthW and a suitable height H. This operation fills in the gaps and removesthe noise as each of the image mask values is replaced by the medianvalue in its WxH neighborhood window. An example of a resulting mask isshown in FIG. 7b . The resulting mask has the same dimensions as theoriginal cross-sectional image.

In still more detail, in one embodiment of the invention, each scan lineof the mask is processed to find all pairs of start and stop samples asshown in FIG. 6b . The start sample denotes the start of a tissue(foreground) region while the stop sample represents the end of a tissueregion. The thickness of a tissue region is calculated as the number ofsamples between a start sample and a stop sample (i.e. the number ofsamples identified as foreground). A gap region is calculated as thenumber of samples between a stop sample and a start sample (i.e. thenumber of samples identified as background).

In any one scan line it is possible to have more than one regionidentified as tissue, as shown in FIG. 8. This is mainly due to (but notlimited to) blood artifacts, if the lumen is not completely cleared offlowing blood during the image acquisition. To avoid artifacts andselect the pair that best represents the tissue region in a given scanline, a weight is associated with each detected region. The weight, inone embodiment, is calculated as:

Weight=(gap*thickness²)  (1)

so as to favor the thickest isolated region, as blood artifacts arethinner than the imaged vessel wall. It should be appreciated that thisinvention is not limited to this particular weight calculation.

At this point in the procedure, every scan line in a givencross-sectional image should have, at most, one sample that will be onthe lumen contour. The calculated weight associated with the sample onany given scan line is kept for further utilization. Some scan linessuch as those in a side branch of a vessel might not have detectedsamples corresponding to a contour.

A contour segment can be defined, in one embodiment, as a group ofcontiguous scan lines with no discontinuities. A discontinuity is a scanline-to-scan line change in the sample number (offset) that exceeds apredetermined continuity threshold. To identify all possible contoursegments, the method begins by searching for the line with the largestweight among the lines not yet grouped in segments (initially, these areall scan lines in a given cross-sectional image). A segment isidentified by searching for discontinuities clockwise andcounter-clockwise from the line with the largest weight as illustratedin FIG. 9. One way to determine a discontinuity threshold is to computeand smooth a line-to-line change in an offset histogram.

FIG. 10 shows an illustration of a possible smoothed histogram. The costrepresents the line-to-line change of offset, and the count representsthe frequency (the number of occurrences) for a given change of offset.Such a histogram typically has a bi-modal distribution. The peaks withthe lower costs represent acceptable, physiologically feasible changesin offsets, while the peaks with the higher costs represent transitionsto and from artifacts. In FIG. 10, a region of zero count separates thetwo peaks of the bi-modal histogram. The smallest cost with zero countis identified and used as a threshold. It should be noted that thisinvention is not limited to this one particular method for determiningthe discontinuity threshold.

The luminal contour is a possible grouping of one or more contoursegments. The root (first segment to add to the contour) of the contouris selected as the longest valid segment. The nearest clockwise andcounter-clockwise neighboring segments of each potential contour segmentare identified. Valid neighbors must pass an angular distance threshold,a radial distance threshold, and a Euclidian (direct connection)distance threshold. Each potential contour is then traversed clockwiseand counter-clockwise and the longest contour is selected.

To detect and remove the guide wire and other similar artifacts from theimage, an ellipse is fitted to the foreground of a median mask (shown inFIG. 11a ). The area inside of the ellipse is then blanked to remove anysmall disconnected regions as shown in FIG. 11b . Applying the resultingmask to the OCT image, the average intensity value along each scan lineof the masked OCT image is calculated (shown in FIG. 11c as a pluralityof scan lines of varying shading). The guide wire shadow is thenidentified via the use of a suitable gradient filter, such as the Sobeledge detector and the guide wire offset (its radial distance from thecatheter) is detected inside the guide wire shadow region. Shadows fromother sources such as stent struts and residual blood are also detectedand need to be delineated from the guide wire shadow. The midpoints ofall detected shadow regions on all frames is then collected and used asnodes to build a minimum spanning tree. In one embodiment of theinvention, the nodes of the tree are selected and connected such that:no points on the same frame are connected together; and any given nodeis connected to a parent node that minimizes a weight value. In oneembodiment the weight value is calculated as the sum of the distance andslope difference between a node and its parent node. A sample resultingtree is shown on the L-mode display in FIG. 11d . Finally, the tree ispruned by removing small branches (according to a suitable threshold) asshown in FIG. 11 e.

Missing contour data is interpolated as shown in FIGS. 1 and 2. In oneembodiment, a smooth curve between two points is interpolated using thecosine function. The range of values of a cosine function is +1 to −1inclusive in the domain 0 to π. Since the interpolation between twopoints requires a weighting range from 0 to 1 inclusive, it is desirableto adjust the cosine range. Using the function (1-cos) provides a rangefrom 0 to 2 inclusive and dividing by 2 yields (1-cos)/2 with therequired range from 0 to 1.

Alternatively, one can use any suitable function such as the cubicfunction or the Hermite function to interpolate missing data using fouror more control points instead of two. Interpolating a point between twopoints y₁=f(x₁) and y₂=f(x₁+Δx), calculates the value of the point on apreselected curve between x₁ and x₂. The general relation is given by(1−α)y₁+(α)y₂, where α is the interpolation weight ranging from 0 at x₁to 1 at x₁+Δx. Using the previously described cosine weighting method,the weight of a point at given distance d from x₁ is calculated byα+(1−cos(π*d/πx))/2. It should be noted that this invention is notlimited to any one particular interpolation method.

For an entire longitudinal segment of interest for a vessel, an areagraph vs. longitudinal position is constructed from the individuallycalculated cross-sectional areas as shown in FIG. 12. For any missingdata (where the contour extraction might have failed for any reason) asuitable interpolation method can be used. The resulting graph (FIG. 3)is smoothed to remove sharp transitions in the area graph. One way tosmooth the area graph is to use a median filter. It should be noted thatthis invention is not limited by any one particular smoothing method.

Once the cross-sectional area of the vessel has been determined theseverity of any stenotic region is then characterized. One measure ofseverity of a stenotic lesion imaged by OCT is provided by a parametercalled the vascular resistance ratio (VRR). The VRR quantifies the bloodflow resistance of a stenotic vessel segment relative to the flowresistance of the entire vessel branch, assuming maximum vasodilation ofthe peripheral coronary vasculature. The VRR is defined as:

$\begin{matrix}{{V\; R\; R} \equiv \frac{R_{s}}{R_{T}}} & (2)\end{matrix}$

where R_(s) is the blood flow resistance of the stenotic segment andR_(T) is the total flow resistance of the branch vessel in which thestenotic region is located. VRR ranges from 0 (no vessel narrowing) to 1(all flow resistance due to the stenosis).

The calculation of VRR is based on a lumped parameter model (FIG. 13) ofthe blood flow through a stenosed branch of a coronary artery underhyperemic conditions. In this model, the blood flow Q, driven by thedifference between the arterial blood pressure P_(a) and the coronaryvenous pressure P_(v), is limited by the total flow resistance (R_(T))of the branch of the vessel through which the blood is flowing. R_(T) iscomposed of the sum of three resistance elements,

R_(T)=R_(s)+R_(e)+R_(mv)  (3)

where R_(s) is the blood flow resistance of the stenotic segment, R_(e)is the blood flow resistance of the remaining epicardial length of thebranch, and R_(mv) is the microvascular resistance of the peripheralcoronary vascular bed.

In general, the values of all three resistance elements depend on bloodflow, but only R_(S) is shown explicitly as a function of Q, becauseR_(mv), and R_(e) are only weakly flow-dependent under conditions ofmaximum vasodilation. During drug-induced hyperemia, R_(mv) isapproximately constant and is given by:

$\begin{matrix}{R_{mv} = \frac{P_{a} - P_{v}}{Q_{\max}}} & (4)\end{matrix}$

where Q_(max) is the maximum blood flow that can be achieved in thebranch when the pressure drop across the epicardial arteries isnegligible (i.e., R_(s)+R_(e)→0). Q_(max) equals the product of the meanhyperemic Doppler blood velocity, v_(max), measured in a normalreference segment of the artery and the cross-sectional area, A_(n), ofthe artery measured in the same location, Q_(max)=v_(max)A_(n). Velocitymay also be measured using speckle caused by particulates in the streamand detected in the OCT image. Based on these relationships, Eqn. 4 canbe re-formulated in terms of hyperemic velocity:

$\begin{matrix}{R_{mv} = {\left( \frac{P_{a} - P_{v}}{v_{\max}} \right) \cdot \frac{1}{A_{n}}}} & (5)\end{matrix}$

The quantity in braces, which has units of mm Hg cm⁻¹s, is the hyperemicmicrovascular resistance index, designated as h-MRv. An importantadvantage of determining hyperemic resistance using velocity instead offlow is that velocity normalizes flow for differences in arterialdiameter due to branching and is preserved between proximal and distalsegments. Table 1 lists published values of h-MRv measured during PCIwith a Doppler flow wire. The values lie within a relatively narrowrange for both treated and untreated vessels.

In the calculations shown it is assumed that h-MRv is a constantapproximately equal to 1.0 mm Hg cm⁻¹s, a value that lies at the lowerend of the distribution of resistances in Table 1 for upsized stentedarteries. The value of A_(n) in Eq. 5 is assumed to equal thecross-sectional area of the proximal segment of the reference vessel.For a 3-mm diameter artery, Eqn. 5 yields R_(mv)=17 mm Hg cm⁻³s with acorresponding maximum flow of about 4.7 ml/s at an arterio-venouspressure difference of 80 mmHg.

The second component of the total resistance in Eqn. 3, R_(e), theepicardial resistance outside of the stenotic segment of the vessel, isusually small compared to R_(s) and R_(mv). Its value can be estimatedby integrating the flow resistance along the length of the vessel,L_(e)=L_(T)−L_(s) where L_(T) is the total length of the coronary branchand L_(s) is the length of the stenotic segment imaged by OCT. Assumingthat no significant flow-limiting stenoses are present outside of thestenotic segment and that the mean cross-sectional area of the vesselremains the same as in the mean cross-sectional area, Ā_(n), of thereference segments adjacent to the stenosis imaged by OCT, R_(e) can becalculated using Poiseuille's law, as

$\begin{matrix}{{R_{e} = \frac{8\pi\eta L_{e}}{{\overset{\_}{A}}_{n}^{2}}},} & (7)\end{matrix}$

where η is the viscosity of the blood and the mean area is given by

$\begin{matrix}{{\overset{\_}{A}}_{n} = {\frac{1}{M}{\sum\limits_{i = 1}^{M}A_{i}}}} & (8)\end{matrix}$

In this equation, the cross-sectional lumen areas A are measured in theframes of the OCT image located outside of the stenotic region, so thatthe total number of available frames M depends on the lengths of theproximal and distal reference segments in the image. Although the totallengths of the epicardial coronary branches are not, in general, thesame, it is assumed that L_(T)=8 cm for the main coronary arteries (LAD,LCX, and RCA), so that L_(e) can be found directly by subtracting thelength of the OCT image region from L_(e). A better estimate of theepicardial length can be obtained from lengths measured by angiography,if such data is available. The mean area is estimated as the average ofthe diameters of the proximal and distal reference segments.

Calculation of the stenotic resistance, R_(s), in Eqn. 3 is complicatedby its dependence on blood flow. R_(s) is composed of a flow-independentcomponent that results from viscous losses and a flow-dependentcomponent that results from kinetic losses. A variety of methods havebeen developed for calculation of the flow resistance of stenoticlesions. Three different embodiments of methods (one analytical and twonumerical) by which R_(s) can be calculated based on measurements oflumen morphology by OCT will now be discussed.

The first embodiment of a method for calculation of R_(s) is adaptedfrom a model of pressure loss in stenotic lesions developed byKirkeeide. FIG. 14 illustrates the cylindrically symmetrical geometry onwhich the model is based. The total resistance of the stenosis isassumed to consist of two flow-independent components and aflow-dependent component:

R_(s)=R_(p)+R_(v) +k _(e)Q  (9)

Here R_(p) represents losses due to viscous wall friction, calculatedaccording to Poiseuille's law as:

$\begin{matrix}{R_{p} = {8\pi\eta{C_{1}\left\lbrack {{\sum\limits_{i = 1}^{N}\frac{\Delta\; x_{i}}{A_{i}^{2}}} - {\sum\limits_{({{Exit}{regions}})}\frac{\Delta\; x_{i}}{A_{i}^{2}}}} \right\rbrack}}} & (10)\end{matrix}$

This resistance equals the total integrated viscous losses along thevessel minus the losses in the exit regions where flow separationoccurs. Exit regions are defined as the segments of the artery withinwhich the exit angle (θ in FIG. 14) exceeds a threshold value (typically5°). In these equations C₁=0.86, based on results of experimentsconducted by Kirkeeide.

The second flow-independent component of R_(s) in Eq. 9, whichrepresents the additional viscous losses that occur at the entrance ofregions of sudden narrowing of the vessel wall, is given by:

$\begin{matrix}{R_{v} = {8\pi\eta{C_{2}\left\lbrack \frac{d_{p}}{A_{m}^{2}} \right\rbrack}}} & (11)\end{matrix}$

where d_(p) is the diameter of the artery on the proximal side of thestenosis, A_(m) is the minimum lumen area of the stenosis, C₂=0.45.

The flow-dependent component of R_(s) in Eq. 9 includes losses due toflow separation and recirculation at the exit of narrowed regions of theartery. At high flow rates and in vessels with highly irregular crosssections, the effective resistance of a blood vessel can significantlyexceed that predicted by Poiseuille's law, which is based on analysis oflaminar flow of a Newtonian fluid through a straight cylinder. Accordingto Kirkeeide:

$\begin{matrix}{k_{e} = {\frac{C_{3}\rho}{2}\left( {\frac{1}{A_{m}} - \frac{1}{A_{d}}} \right)^{2}}} & (12)\end{matrix}$

where ρ is the mass density of the blood, A_(d) is the area of theartery distal to the stenosis, and

$\begin{matrix}{{C_{3} = {{{1.2}1} + {{0.0}8\frac{\ell_{s}}{d_{d}}}}},} & (13)\end{matrix}$

Here

s is the length of the stenosis, defined as the region between the wallangle inflection points on either side of the stenosis (FIG. 14), andd_(d) is the diameter of the artery on the distal side of the stenosis.This equation accounts for the increase in expansion losses with lesionlength.

Now that all of the terms in Eq. 9 have been defined, the vascularresistance ratio can be expressed as

$\begin{matrix}\begin{matrix}{{V\; R\; R} = \frac{R_{s}}{R_{s} + R_{e} + R_{mv}}} \\{= \frac{R_{p} + R_{v} + {k_{e}Q}}{R^{\prime} + {k_{e}Q}}}\end{matrix} & (14) \\{with} & \; \\{R^{\prime} = {R_{e} + R_{mv} + R_{p} + R_{v}}} & \left( {15a} \right) \\{and} & \; \\{Q = \frac{\sqrt{{R^{\prime}}^{2} + {4{k_{e}\left( {P_{a} - P_{v}} \right)}}} - R^{\prime}}{2k_{e}}} & \left( {15b} \right)\end{matrix}$

The other embodiments of the method, instead of Kirkeedee's equations,use a numerical Navier-Stokes solver such as FloWorks, (SolidWorksCorporation, Concord, Mass.) or Fluent (Ansys, Ann Arbor, Mich.) orequivalent to calculate the stenotic resistance R_(s) in the model inFIG. 13. The vessel contours are delineated by OCT and the flow withinthe walls is broken into thousands of small volumes. Simultaneously, ateach volume, the Navier—Stokes momentum and conservation of massequations are solved to compute the flow field through the volume. Fromthis flow field the pressure drop along the vessel is found.

In the second embodiment of the method, the cylindrically symmetricalcomputational flow model, the same area—versus— position graphs are usedas in the first embodiment. The Navier-Stokes equations are solvedassuming the shape is a perfect circle at each location along the OCTimage. In the third embodiment, the full-3D computational flow modelbased on the actual OCT lumen contours is used. The wall geometry isbroken into triangles spanning every other frame and every 15° aroundthe catheter. FIGS. 15 and 16 show sections of the geometry on whichblood flow is modeled.

Studies of anatomy show that the sum of the cross sectional area ofbranches derived from a parent is greater than the cross sectional areaof the parent. This minimizes viscous shear stress through theepicardial tree. Based on viscous losses, Murray's law states that thecube of the radius of a parent vessel equals the sum of the cubes of theradii of the daughters. Table 2 shows the area increase calculated byMurray's law when the branches are symmetric.

The steps to obtain the branch sizes are:

The parent vessel area is taken as the proximal area at the referenceplane. One daughter vessel is taken as the distal reference plane. Theinitial guess of the remaining daughter vessel areas is taken from analgorithm that interrogates the OCT image. The radius of the vessels iscalculated, assuming they are circular. These radii are all multipliedby a single scale factor. The scale factor is determined by Murray'slaw. Murray's law is applied one branch at a time. The area remainingafter the most proximal branch area is subtracted is used as the parentarea for the next branch. The remaining area after Murray's law isapplied to the last branch will equal the distal reference area.

With the cylindrically symmetric computational flow model, the flowoutside of the imaged area is not calculated, but instead is calculatedusing the resistance network shown in FIG. 13. R_(s)(Q) is calculatednumerically with the computational flow simulation program with R_(e)and R_(mv) calculated in the same way as in the first embodiment of themethod. R_(e) and R_(mv), are both independent of flow (i.e., produce apressure drop linear with flow). They are simply added as a singleresistor to the numerical simulation. The numerical flow simulatorautomatically adjusts the flow to maintain P_(v)-P_(a).

The reference area, A_(n) in Eqn. 5, is calculated differently for thetwo models. The cylindrically symmetric model (second method) does nothave any branches, therefore A_(n) is calculated based on the average ofproximal and distal areas. Thus, the velocity in the FloWorks geometrywill be an average of the flows that would be encountered through thetapering section. The full 3-D model (third embodiment) includesbranches, therefore A_(n), is calculated based on the proximal areaonly.

The lumped resistor method shown in FIG. 13 is extended for the full 3-DComputational Flow Model in FIG. 24. The resistance of the branches R₁,R₂ . . . R_(N) and R_(Distal) are each composed of the series resistorsR_(e)+R_(mv). The downstream end of every branch resistor is at P_(v)(10 mm Hg). The upstream end of the resistor is at the static pressurethat numerical method calculates at that branch. The input pressure ofthe parent artery at the proximal reference is 90 mm Hg.

R_(e) of each branch is calculated based on the location in the image.Calculation of R_(mv) is more complex. According to Murray's law, thesum of the cross-sectional areas of branches coming off a parent isgreater than the cross sectional area of the parent. Consequently, thevelocity decreases after every branch. This affects R_(mv) for theentire artery and for each branch.

R_(mv) for the entire artery is adjusted by assuming the 1.0 mm Hg cm⁻¹svalue of h-MRv was determined based on a reference diameter of 3.4 mm.For other proximal reference diameters R_(mv) is adjusted downwardsaccording to the ratio of the proximal reference diameter to thereference diameter to the ¼ power. The ¼ power equates pressure dropsthrough the vasculature. Data on the variation of velocity data throughthe coronaries is limited, but the ¼ power rule seems to correlate thepublished data as shown in Table 3. A more sophisticated approach wouldadjust R_(mv) according to the vessel type (LAD: left anteriordescending artery, RCA: right coronary artery, LCx: left circumflex).

Likewise, R_(mv) for each branch is adjusted by the same ¼ power of thediameter ratio of the branches to the reference diameter of 3.4 mm. If abranch is smaller than 2 mm, R_(mv) is taken at 2 mm diameter. R_(mv)for all the daughter branches is summed to insure it adds up to R_(mv)for the proximal reference. If it is different, R_(mv) for all thebranches are scaled equally.

As the numerical program is run, the pressure and flow are obtainedalong the artery length. The slope of the total pressure along thelength can be used to highlight areas of high resistance. The staticpressure along the length can be correlated with pressure measurements.VRR is calculated between any two points of interest, usually the distaland proximal references. Since the flow is calculated, other indicesthat use flow and pressure, such as Stenotic Reserve Index (SRI) can becalculated. Meuwissen et al. defined the Stenosis Resistance Index (SRI)as the slope of this line between two measurement points:

SRI=Pressure Difference Between Measurement Points(dP)/Proximal Velocity

In one embodiment, SRI is calculated by assuming a velocity. Velocity isfairly constant in human arteries. In one study of 32 patients afterpercutaneous coronary intervention PCI, the measured velocity was79±17.2 cm/s. Since the velocity variation is small and the SRI curve isfairly independent of velocity, the estimate of SRI made withoutvelocity measurements can be acceptable.

Velocity is a better way to normalize SRI than flow because pressuredrop is mostly proportional to velocity. If flow is used, it typicallyunderestimates the effect of a stenosis in a large vessel and converselyoverestimates the effect of a stenosis in a small vessel. The velocitythat is selected is the velocity at a reference diameter, not thestenosis velocity. The physician selects the proximal reference and thevelocity measurement is taken there. The resulting SRI will give thephysician the resistance that will be eliminated by the stent.

The flow through the region of interest will change if a side branch isdetected. The flow down the side branch will be estimated from the sidebranch size and the reduction in area from the proximal to distalreference. Both the algebraic equations and the Navier-Stokes Equationare modified to include the side branches.

If SRI is reported, a different SRI will be used than that of Meuwissenet al. This index, termed the LightLab SRI (LSRI) is defined as:

LSRI=Total Pressure Difference/Velocity-Integrated Poiseuille Equation

where: total pressure difference is the static pressure at a firstlocation plus the velocity head (p V₁ ²/2) at the first location minusthe static pressure at a second location plus the velocity head (p V₂²/2) at the second location. The locations typically straddle the regionof interest in the lumen. Velocity, V, is the bulk average velocity. Theintegrated Poiseuille equation is the laminar flow pressure dropcalculated between the reference locations assuming the diameterincreases linearly. This is an improvement over the standard SRImeasurement because the total pressure is more reflective of the truelosses in an artery than the static pressure used in standard SRI andthe integrated Poiseuille equation removes the effects of the distancebetween measurement locations, which is a limitation of standard SRI.

Another parameter that is measurable by this technique is the fractionalflow reserve (FFR). As defined by the model in FIG. 13, the vascularresistance ratio (VRR) has a direct relationship with the fractionalflow reserve (FFR). The FFR is determined from measurements of thepressure distal to a stenosis relative to the arterial pressure:

$\begin{matrix}{{FFR} = \frac{P_{d} - P_{v}}{P_{a} - P_{v}}} & (16)\end{matrix}$

Clinically an FFR value greater than or equal to 0.75 typically isconsidered to mean that treatment is not required. Generally the FFR ismeasured following the administration of drugs that cause a maximumhyperemic response by causing the capillary beds to dilate followed bythe taking of an intravenous pressure measurement.

Assuming that there are no additional stenoses proximal to the stenoticsegment, VRR is inversely proportional to FFR:

$\begin{matrix}\begin{matrix}{{V\; R\; R} = {\frac{R_{s}}{R_{T}} = {\frac{\left( {P_{a} - P_{d}} \right)/Q}{\left( {P_{a} - P_{v}} \right)/Q} = \frac{\left( {P_{a} - P_{d}} \right)}{\left( {P_{a} - P_{v}} \right)}}}} \\{= {1 - {FFR}}}\end{matrix} & (17)\end{matrix}$

A VRR of less than 0.25 means that treatment is not indicated. A benefitof VRR is that, as shown below, a VRR calculation may be made withoutthe use of drugs or the measurement of intravascular pressure.

Once the segmental resistances on which the VRR is based have beencalculated, additional information can be displayed to help theclinician select the length of a stent required to cover a stenoticlesion. One concept for displaying this information is illustrated inFIG. 17. Here, to provide feedback about the lesion length, the segmentof the artery centered on the MLA plane that encompasses auser-selectable fraction κ (typically 0.9≤x≤0.95) of the total vascularresistance is highlighted. In mathematical terms, the length of thehighlighted region, 2ΔL, centered on the MLA position

⁰ determined such that the relationship

$\begin{matrix}{{\sum\limits_{N{({\ell_{0} - {\Delta\; L}})}}^{N{({\ell_{0} + {\Delta\; L}})}}R_{i}} \geq {\kappa\; R_{m}}} & (18)\end{matrix}$

is satisfied. Here N(

₀−ΔL) and N(

₀+ΔL) are the frame numbers at the distal and proximal limits of thevessel segment. Alternatively, the high-resistance regions can beidentified independently of the location of the MLA cross section bysorting the resistances of the incremental segments from highest tolowest and highlighting only those segments at the top of the list thatsum to a user-selectable fraction of the total vascular resistance. Theadvantage of this method is that more than one region of high resistancein a diffusely narrowed artery can be identified readily, as shown bythe example in FIG. 18.

Once the parameters of vessel size and blood flow resistance arecalculated, the present invention also provides methods for optimizingstent choice and placement automatically or semi-automatically viainteractive commands. These flow calculations, when combined with a setof a priori constraints, enable a cardiologist to optimize the length,diameter, and longitudinal position of a stent before implantation.

Referring again to FIG. 5, a three-dimensional (3D) image of the lumenof a coronary artery derived from OCT image data is depicted. Togenerate this image, the contours of the wall of the lumen are tracedautomatically by computer software described above. The morphologicaldata represented by the three-dimensional image of the lumen provide thestarting point for various embodiments of the stent optimizationprocedure. The first image-processing step reduces the 3D data set to acylindrically symmetrical data set that shows the mean diameter of eachcross section along the axis of the catheter. The mean diameter D ateach longitudinal position x is calculated as the diameter of a circlewith the same area as the cross-section,

$\begin{matrix}{{D(x)} = {2\sqrt{\frac{A(x)}{\pi}}}} & (1)\end{matrix}$

where A(x) is the area of the cross section. Alternatively, the meandiameter can be found by averaging the lengths of chords drawn throughthe centroid of the lumen cross section. FIGS. 19a and 19b show examplesof displays of mean-diameter for an OCT image of a coronary artery. InFIG. 19a , the branches of the artery are shown as perpendicular barswith widths equal to the widths of the ostia of the branches, while inFIG. 19b , the vessel branches are shown as circles with diameters tothe widths of the ostia of the branches.

For interactive stent optimization, the mean-diameter display shows theposition of a reconfigurable stent superimposed on the vessel profile,as illustrated in FIG. 20. The expanded diameter, length, andlongitudinal position of the stent are the main variables that determinethe effectiveness of the stent in restoring the available blood flow tothe heart muscle. The present invention employs the difference betweenthe calculated values of the vascular resistance ratio (VRR) before andafter stenting as a key stent optimization parameter. Another importantoptimization parameter is the maximum stent malapposition distance,defined as the widest separation between the surface of the stent strutsand the vessel wall over the entire length of the stent. Minimization ofthis distance, especially for drug-eluting stents, is necessary toassure that the stent is affixed firmly to the vessel wall and that thestent provides adequate radial support to prevent collapse of thevessel. A third important optimization parameter is the degree ofoverlap of the stent and the ostia of side branches. Minimal overlap isdesirable to avoid blockage of blood flow to branches as a result ofthrombus formation or growth of new tissue on the stent struts.

The various embodiments of the present invention provide methods forchoosing the optimal stent length, diameter, and longitudinal positionin accordance with the aforementioned optimization parameters (VRR,malapposition distance, branch overlap, presence of calcium, etc.). Theflow chart in FIG. 21 outlines the optimization procedure associatedwith one specific embodiment. In this embodiment, the user chooses adesired stent length, L_(fixed), and the optimization proceedsiteratively to find the longitudinal position of the stent, x_(opt) anddiameter of the stent, D_(opt), that minimizes VRR while maintaining amalapposition distance, ε, less than a maximum allowable distance,ε_(max), and a stent diameter less than D_(max). Typically ε_(max) isfixed at a small value between 0 and a value deemed clinicallyinsignificant (e.g., 0.1 mm) and D_(max) is set equal to the maximumdiameter of the vessel measured within the imaged segment plus one stentdiameter increment (typically 0.25 mm). To accelerate the iteration, thesets of available stent diameters {D_(min)≤D≤D_(max)} and stentpositions {0≤x≤(L-L_(fixed))} are limited to discrete values separatedby clinically significant increments. Further acceleration of theoptimization can be achieved by employing a multivariate look-up tableof stent diameters and stent positions instead of linear arrays ofvariables. Although not shown in flow chart in FIG. 21, additionalconstraints, such as the degree of overlap with side branches andcalcified regions, are included within the scope of the invention.

In addition to reporting the recommended diameter and position of thestent to the user, this specific embodiment of the optimizationprocedure also reports the predicted values of VRR_(opt), the vascularresistance ratio, and ε_(r), the residual malapposition distance. If theuser deems these values to be unsatisfactory, the optimization can berepeated with a longer stent length as an input. In this way, errors inthe sizing and positioning of stents can be avoided before implantation.

FIG. 22 outlines the steps of an embodiment of a fully automaticoptimization procedure in which the diameter, length, and longitudinalposition are optimized simultaneously. Here the user inputs only atarget VRR value, VRR_(max), and the optimization then proceedsiteratively to find the shortest stent that achieves the desired bloodflow resistance under the constraints imposed on maximum diameter andmaximum malapposition distance.

In more detail, the system first creates arrays of area and diameter foreach cross-section along the unstented vessel. Next, the system createsa lookup table that has the available ranges of stent diameter, lengthand position. Then, progressing through each entry in the lookup table,the system calculates the VRR and maximum malapposition value. Themaximum malapposition value equals the distance between the maximumunstented diameter in the segment and the diameter of the stent. Tableentries that result in VRR values less than VRR_(max) and the maximummalapposition values are retained and then the stent length for eachsubset is determined. The table entry in which the stent length is aminimum defines the optimal stent parameters.

To be useful as an interactive bed side tool, the recalculation of VRRfor a selected stent size needs to be almost instantaneous. The mostaccurate method to find the chosen stent effect of VRR would be to firstmeasure or calculate VRR on the unstented artery using the OCTmeasurements above or a finite element computational fluid dynamicsprogram and then recalculate VRR using the same finite elementcomputational fluid dynamics program on the proposed stented arteryshape. However, most computational fluid dynamics programs will not runfast enough on typical computers to quickly show the affect of theproposed stent. A method is needed to have the accuracy of computationalfluid dynamics but allow the rapid recalculation of VRR with theproposed placement of a stent.

A hybrid approach is disclosed here that allows for rapid recalculation.In the region of the proposed stent, algebraic equations are used todetermine pressure drop. In the regions outside of the stent, thepreviously obtained measured or computational fluid dynamics solution isused, modified by the effect of the stent. The rapid recalculation isobtained by only using algebraic equations during the stent sizing. Oncethe stent sizing is complete, a full computational fluid dynamicssimulation may be run to obtain an even more accurate answer.

The initial calculation of VRR on the unstented artery is done using afinite element computational fluid dynamics program. Since there is sometime between the end of the imaging procedure and the start of the stentplacement, the amount of time this calculation takes is not a limitingconstraint. An important output of the computational fluid dynamicsprogram is a total pressure versus distance graph as shown in the FIG.23. The simplest way to calculate the change in VRR from the proposedstent addition is simply to subtract the pressure drop in the stentedarea as shown. The VRR display is updated as the stent length andlocation are changed by the operator.

A more sophisticated approach takes into account that the pressure dropoutside of the proposed stented area will increase because the flowincreases with the elimination of the stenosis. FIG. 24 shows anequivalent resistor network model of the pressure drops through theartery. The total pressure drop graph from FIG. 23 is broken up intoequivalent flow resistors, each spanning a branch or the artery. R₀₋₁ isthe flow resistance from the proximal end of the OCT image to the firstbranch, R₁₋₂ is between the first and second branches, and R_(D-N) isbetween the last branch and the distal end of the OCT scan. If a stentis placed in one of the resistors, the pressure drop in that resistor ismodified as follows. First, the calculated pressure drop from thestenosis is set to zero in the stent. The Poiseuille pressure dropthrough the length of the stent is added and the losses at the entranceand exit of the stent due to the diameter change are added. The flowcalculated with the stenosis by computational fluid dynamics is used toset the resistor values.

The resistor network in FIG. 24 can be solved by using equations forresistors in series and parallel. An explicit series of equations forflow and thus pressure drop in the stented artery can then be found. Theflow division between the branches is readjusted from the resistornetwork. The flow resistances may be considered linear with flow as afirst approximation. A more sophisticated approximation will include thenon-linear response of pressure drop with flow. The new value of VRR isdisplayed on the screen as the stent is resized. This calculationhappens rapidly as it is simply algebraic equations. This value of VRRis marked as preliminary. The full computational fluid dynamicssimulation takes place during the stent resizing and when thecalculation is complete the VRR value is marked as final.

Target values of VRR can be established according to results ofpublished clinical studies. For example, the results of one influentialstudy showed that adverse event rates in patients with a single stentedlesion were reduced significantly when the fractional flow reserve (FFR)measured in the stented artery was in the range 0.96-1.0 compared to theadverse event rates of a similar population of patients with measuredFFR values in the range 0.9-0.95. Therefore, FFR_(min)=0.96 is apost-stent target supported by clinical evidence. According to itsdefinition, VRR has a simple inverse relationship with fractional flowreserve (VRR=1−FFR); it follows that, based on this study, anappropriate target maximum value of is VRR_(max)=1−0.96=0.04.

FIGS. 25 and 26 depict the output results of the specific embodiments ofthe invention. FIGS. 25a and 25b show the pre- and (predicted)post-stented mean-diameter lumen profiles resulting from thefixed-stent-length optimization procedure for two different stentlengths, L_(fixed)=8 mm and L_(fixed)=24 mm. The input data were derivedfrom a sequence of OCT images that was recorded in vivo from a branch ofa patient's coronary artery. In this example, the optimization proceduredetermined the diameters and longitudinal positions of the stents thatminimized the hyperemic blood flow resistance, while maintaining goodstent apposition. The predicted residual gaps between the stent and thevessel wall for L_(fixed)=24 mm are shown in FIG. 26 as blank regions

FIGS. 26a and 26b show the pre- and (predicted) post-stentedmean-diameter lumen profiles resulting from the fully automaticoptimization procedure for two different target VRR values,VR_(Rmax)≤0.05 and VRR_(max)≤0.02 Again, the input data were derivedfrom a sequence of OCT images recorded in vivo from a branch of apatient's coronary artery. The procedure determined the longitudinalpositions, diameters, and minimum lengths of the stents required toreduce VRR below the target values, while maintaining good appositionbetween the stent and the vessel wall.

FIG. 27 shows a computer interface with a three dimensional depiction inthe top panel of a stent that is not properly placed in the lumen ofinterest. Two regions of stent malapposition are shown as hatchedregions. Thus, in one embodiment, the methods of the invention andfeatures described herein are directed to a computer-based userinterface that allows views of OCT in multiple panels. Further, stentmalapposition can be shown in three-dimensions. In addition, in the caseof stimulated stent placement, the user may reposition the stent toremove the areas of malapposition to simulate proper stent placementprior to implanting a stent in a real patient

The present invention may be embodied in many different forms,including, but in no way limited to, computer program logic for use witha processor (e.g., a microprocessor, microcontroller, digital signalprocessor, or general purpose computer), programmable logic for use witha programmable logic device, (e.g., a Field Programmable Gate Array(FPGA) or other PLD), discrete components, integrated circuitry (e.g.,an Application Specific Integrated Circuit (ASIC)), or any other meansincluding any combination thereof. In a typical embodiment of thepresent invention, some or all of the processing of the data collectedusing an OCT probe and the processor-based system is implemented as aset of computer program instructions that is converted into a computerexecutable form, stored as such in a computer readable medium, andexecuted by a microprocessor under the control of an operating system.Thus, query response and input data are transformed into processorunderstandable instructions suitable for generating OCT data, histologyimages, OCT images, vascular resistance, overlays masks, signalprocessing, weighting artifact removal, contour detection and otherfeatures and embodiments described above.

Computer program logic implementing all or part of the functionalitypreviously described herein may be embodied in various forms, including,but in no way limited to, a source code form, a computer executableform, and various intermediate forms (e.g., forms generated by anassembler, compiler, linker, or locator). Source code may include aseries of computer program instructions implemented in any of variousprogramming languages (e.g., an object code, an assembly language, or ahigh-level language such as Fortran, C, C++, JAVA, or HTML) for use withvarious operating systems or operating environments. The source code maydefine and use various data structures and communication messages. Thesource code may be in a computer executable form (e.g., via aninterpreter), or the source code may be converted (e.g., via atranslator, assembler, or compiler) into a computer executable form.

The computer program may be fixed in any form (e.g., source code form,computer executable form, or an intermediate form) either permanently ortransitorily in a tangible storage medium, such as a semiconductormemory device (e.g., a RAM, ROM, PROM, EEPROM, or Flash-ProgrammableRAM), a magnetic memory device (e.g., a diskette or fixed disk), anoptical memory device (e.g., a CD-ROM), a PC card (e.g., PCMCIA card),or other memory device. The computer program may be fixed in any form ina signal that is transmittable to a computer using any of variouscommunication technologies, including, but in no way limited to, analogtechnologies, digital technologies, optical technologies, wirelesstechnologies (e.g., Bluetooth), networking technologies, andinternetworking technologies. The computer program may be distributed inany form as a removable storage medium with accompanying printed orelectronic documentation (e.g., shrink-wrapped software), preloaded witha computer system (e.g., on system ROM or fixed disk), or distributedfrom a server or electronic bulletin board over the communication system(e.g., the Internet or World Wide Web).

Hardware logic (including programmable logic for use with a programmablelogic device) implementing all or part of the functionality previouslydescribed herein may be designed using traditional manual methods, ormay be designed, captured, simulated, or documented electronically usingvarious tools, such as Computer Aided Design (CAD), a hardwaredescription language (e.g., VHDL or AHDL), or a PLD programming language(e.g., PALASM, ABEL, or CUPL).

Programmable logic may be fixed either permanently or transitorily in atangible storage medium, such as a semiconductor memory device (e.g., aRAM, ROM, PROM, EEPROM, or Flash-Programmable RAM), a magnetic memorydevice (e.g., a diskette or fixed disk), an optical memory device (e.g.,a CD-ROM), or other memory device. The programmable logic may be fixedin a signal that is transmittable to a computer using any of variouscommunication technologies, including, but in no way limited to, analogtechnologies, digital technologies, optical technologies, wirelesstechnologies (e.g., Bluetooth), networking technologies, andinternetworking technologies. The programmable logic may be distributedas a removable storage medium with accompanying printed or electronicdocumentation (e.g., shrink-wrapped software), preloaded with a computersystem (e.g., on system ROM or fixed disk), or distributed from a serveror electronic bulletin board over the communication system (e.g., theInternet or World Wide Web).

Various examples of suitable processing modules are discussed below inmore detail. As used herein a module refers to software, hardware, orfirmware suitable for performing a specific data processing or datatransmission task. Typically, in a preferred embodiment a module refersto a software routine, program, or other memory resident applicationsuitable for receiving, transforming, routing and processinginstructions, or various types of data such as OCT scan data,interferometer signal data, clock signals, region of interest types,formulas, and other information of interest.

Computers and computer systems described herein may include operativelyassociated computer-readable media such as memory for storing softwareapplications used in obtaining, processing, storing and/or communicatingdata. It can be appreciated that such memory can be internal, external,remote or local with respect to its operatively associated computer orcomputer system.

Memory may also include any means for storing software or otherinstructions including, for example and without limitation, a hard disk,an optical disk, floppy disk, DVD (digital versatile disc), CD (compactdisc), memory stick, flash memory, ROM (read only memory), RAM (randomaccess memory), DRAM (dynamic random access memory), PROM (programmableROM), EEPROM (extended erasable PROM), and/or other likecomputer-readable media.

In general, computer-readable memory media applied in association withembodiments of the invention described herein may include any memorymedium capable of storing instructions executed by a programmableapparatus. Where applicable, method steps described herein may beembodied or executed as instructions stored on a computer-readablememory medium or memory media. These instructions may be softwareembodied in various programming languages such as C++, C, Java, and/or avariety of other kinds of software programming languages that may beapplied to create instructions in accordance with embodiments of theinvention.

While the present invention has been described in terms of certainexemplary preferred embodiments, it will be readily understood andappreciated by one of ordinary skill in the art that it is not solimited, and that many additions, deletions and modifications to thepreferred embodiments may be made within the scope of the invention ashereinafter claimed. Accordingly, the scope of the invention is limitedonly by the scope of the appended claims.

TABLE 1 Reference Stented Upsize stented vessel Balloon lesion lesion1.73 ± 0.38 1.72 ± 0.53 1.58 ± 0.61 1.32 ± 0.39 (n = 20) (n = 19) (n =24) (n = 11) 1.75 ± 0.37 1.59 ± 0.38 1.49 ± 0.41 1.29 ± 0.40 (n = 13) (n= 12) (n = 15) (n = 10) 1.52 ± 0.40 (n = 10) 1.82 ± 0.44 1.67 ± 0.73 (n= 23) (n = 29)

TABLE 2 Area Increase After a Branch Bifurcation Area IncreaseTrifurcations Angiography Study 1.214 Patients without coronary (n = 12)artery disease 1.30 1.12 Left main of patients without (n = 20) coronarydisease 1.26 1.44 N/A

TABLE 3 Proximal End of Artery Distal End of Artery LAD LCx RCA LAD LCxRCA Peak 104 79 72 70 71 67 Velocity (cm/s) Diameter 3.5 3.1 3.4 2 2 2(mm) Peak Vel/67 1.55 1.18 1.07 1.04 1.06 1.00 V/ D{circumflex over( )}0.25/56.5 1.35 1.05 0.94 1.04 1.06 1.00

1. A method for identifying features of a coronary artery, comprising:generating, by the one or more processors, a 3D representation of avessel that is based on vessel image data; providing for display, by theone or more processors, the 3D representation of the vessel comprisingan indication of vessel narrowing, a proximal indicator that is locatedproximally relative to the vessel narrowing, and a distal indicator thatis located distally relative to the vessel narrowing, wherein thedisplay is configured to receive user input adjusting the proximalindicator and the distal indicator; simulating, by the one or moreprocessors, stenting within the vessel between the proximal indicatorand the distal indicator; calculating, by the one or more processors,one or more hemodynamic values based on the stenting; and providing fordisplay, by the one or more processors, information relating to thesimulation of the stenting.
 2. The method of claim 1, wherein thehemodynamic values comprise at least one of a vascular resistance ratioor a fractional flow reserve.
 3. The method of claim 1, whereinsimulating the stenting comprises the use of at least one of a resistormodel or a computational fluid dynamics model.
 4. The method of claim 1,wherein calculating the one or more hemodynamic values is based on amicrovascular resistance of peripheral coronary vasculature.
 5. Themethod of claim 1, wherein calculating the one or more hemodynamicvalues is based on identification of a vessel type.
 6. The method ofclaim 5, wherein the vessel type is one of: a left anterior descendingartery, right coronary artery, and a left circumflex.
 7. The method ofclaim 1, wherein the indication of vessel narrowing identifies alocation of minimum lumen area.
 8. The method of claim 1, wherein theinformation relating to the simulation of the stenting comprisesdisplaying one or more hemodynamic values in connection with arepresentation of the vessel.
 9. The method of claim 1 furthercomprising: receiving, by the one or more processors, user input for analtered stenting; re-calculating, by the one or more processors, one ormore updated hemodynamic values based on the altered stenting; andproviding for display, by the one or more processors, the one or moreupdated hemodynamic values.
 10. A system for identifying features of acoronary artery, comprising: memory; one or more processors incommunication the memory, the one or more processors configured to:generate a 3D representation of a vessel that is based on vessel imagedata; provide for display the 3D representation of the vessel comprisingan indication of vessel narrowing, a proximal indicator that is locatedproximally relative to the vessel narrowing, and a distal indicator thatis located distally relative to the vessel narrowing, wherein thedisplay is configured to receive user input adjusting the proximalindicator and the distal indicator; simulate stenting within the vesselbetween the proximal indicator and the distal indicator; calculate oneor more hemodynamic values based on the stenting; and provide fordisplay information relating to the simulation of the stenting.
 11. Thesystem of claim 10, wherein the hemodynamic values comprise at least oneof a vascular resistance ratio or a fractional flow reserve.
 12. Thesystem of claim 10, wherein in simulating the stenting the one or moreprocessors are further configured to use at least one of a resistormodel or a computational fluid dynamics model.
 13. The system of claim10, wherein calculating the one or more hemodynamic values is based on amicrovascular resistance of peripheral coronary vasculature.
 14. Thesystem of claim 10, wherein calculating the one or more hemodynamicvalues is based on identification of a vessel type.
 15. The system ofclaim 14, wherein the vessel type is one of: a left anterior descendingartery, right coronary artery, and a left circumflex.
 16. The system ofclaim 10, wherein the indication of vessel narrowing identifies alocation of minimum lumen area.
 17. The system of claim 10, wherein theinformation relating to the simulation of the stenting comprisesdisplaying one or more hemodynamic values in connection with arepresentation of the vessel.
 18. The system of claim 10, wherein theone or more processors are further configured to: receive user input foran altered stenting; re-calculate one or more updated hemodynamic valuesbased on the altered stenting; and provide for display the one or moreupdated hemodynamic values.
 19. A non-transitory computer-readablemedium storing instructions executable by one or more processors forperforming a method of identifying features of a coronary artery,comprising: generating a 3D representation of a vessel that is based onvessel image data; providing for display the 3D representation of thevessel comprising an indication of vessel narrowing, a proximalindicator that is located proximally relative to the vessel narrowing,and a distal indicator that is located distally relative to the vesselnarrowing, wherein the display is configured to receive user inputadjusting the proximal indicator and the distal indicator; simulatingstenting within the vessel between the proximal indicator and the distalindicator; calculating one or more hemodynamic values based on thestenting; and providing for display information relating to thesimulation of the stenting.